Prenatal loss is a common occurrence. The survival probability of human conceptions from fertilization to term is estimated to be less than 25% (Roberts & Lowe, 1975). Vatten et al. described a primary male-to-female ratio of 120-165:100 at the time of fertilization, but the ratio decreases to 106:100 at the time of birth. This suggests that prenatal loss concerns males more than that of females, albeit the underlying mechanism is not clear.
There have always been interests and efforts in discovering the contribution of genetic factors to pregnancy loss. A conventional approach is to use population genetics to assess sex-specific prenatal loss. This population genetic approach involves genotyping women experiencing repeated pregnancy loss. Although some positive findings were obtained, the results have been inconsistent. Even if positive findings were obtained, whether miscarriages represent the whole spectrum of repeated pregnancy loss is doubtful. Miscarriages represent only a fraction of the total prenatal loss, and thus rendering the past studies underpowered. Thus, the population genetic approach is suboptimal at best.
Single nucleotide polymorphism (SNP) is a common form of genetic polymorphisms. SNP may influence gene functions and modifies an individual's susceptibility to diseases. Almost any diseases have a genetic component in its etiology and most are being unraveled in genetic association studies. In some instances, a single SNP may be sufficient to confer susceptibility, while in others multiple SNPs may act jointly to influence disease susceptibility. An estimated 20 million SNPs are present in human genome. This astronomical number precludes individual screening one at a time because of the huge work and cost.
To the best of the present inventors' knowledge, there are no reliable genetic markers for prenatal selection (i.e., fetal survival) that have clinical utility. Genetic tests used in in vitro fertilization (IVF) clinics in pre-implantation genetic screening do not contain a genetic marker to predict the survival probability of pregnancy but screens for chromosomal abnormality.
Accordingly, there is a continuing need for a genetic marker to predict the probability of pregnancy success as well as sex-specific prenatal selection. The need for a reliable SNP biomarker for sex-specific prenatal selection is expected to have utility in the application in IVF and infertility clinics.